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The Justy mutant mouse strain produces a spontaneous murine model of salivary gland cancer with myoepithelial and basal cell differentiation
Journal article   Open access   Peer reviewed

The Justy mutant mouse strain produces a spontaneous murine model of salivary gland cancer with myoepithelial and basal cell differentiation

Andrean L Simons, Ping Lu, Katherine N Gibson-Corley, Robert A Robinson, David K Meyerholz and John D Colgan
Laboratory investigation, Vol.93(6), pp.711-719
06/2013
DOI: 10.1038/labinvest.2013.62
PMCID: PMC3669254
PMID: 23608756
url
https://doi.org/10.1038/labinvest.2013.62View
Published (Version of record) Open Access

Abstract

We previously identified a novel mutant mouse strain on the C3HeB/FeJ background named Justy . This strain bears a recessive mutation in the Gon4l gene that greatly reduces expression of the encoded protein, a nuclear factor implicated in transcriptional regulation. Here, we report that Justy mutant mice aged 6 months or older spontaneously developed carcinomas with myoepithelial and basaloid differentiation in salivary glands with an incidence of ~25%. Tumors developed proximate to submandibular glands and to a lesser extent in the sublingual and parotid glands. Histologically, tumors often had central cavitary lesions filled with necrotic debris that was lined by tumors cells and had spindle and epithelioid cell differentiation with lesser basaloid to clear cell features. Tumor tissue often had variable evidence of a high mitotic rate, pleomorphism and invasion into adjacent salivary glands. Neoplastic cells had diffuse immunoreactivity for pancytokeratin (AE1/AE3) and p63. While CK5/6 immunostaining was seen in the much of the tumor cells, it was often lacking in pleomorphic areas. Tumor cells lacked immunoreactivity for alpha -smooth muscle actin, S100, c-Kit and glial fibrillary acid protein. Additionally, tumors had immunoreactivity for phosphorylated and total epidermal growth factor receptor (EGFR), suggesting that EGFR signaling may participate in growth regulation of these tumors. These findings indicate that the salivary gland carcinomas occur spontaneously in Justy mice and that these tumors may offer a valuable model for study of EGFR regulation. Combined, our data suggest that Justy mice warrant further investigation for use as a mouse model for human salivary gland neoplasia.

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